The goal of this program is to develop an improved understanding of metabolic differences between tumors and normal tissue, prior to and after initiation of anti-cancer therapy. The practical objective is to determine how these functional differences lead to useful strategies for differentiating tissues based on biochemical characteristics, and then to learn how this information can be applied for better selection of individualized treatment for a patient. The ultimate goal is to use metabolic imaging information to achieve improved treatment outcome for each patient. Clinical cancer research and tumor biology research are complementary parts of each project. All of the projects investigate ways in which metabolic imaging can contribute to more effective treatment of the patient with cancer, as well as to our understanding of mechanisms by which therapy kills or fails to kill tumors. The projects all use positron emission tomography (PET) to provide quantitative imaging information from the whole body and also data on regional heterogeneity. The team of investigators is strongly interdisciplinary. It draws together experts in oncology, nuclear medicine, radiology, radiobiology, neurology and biochemistry, as well as kinetic modeling, statistics, physics, and radiochemistry. The hypothesis that tumor metabolism is a sensitive measure of response to therapy is a broad one. We have chosen to focus on selected aspects that appear most likely to be important and useful indicators of tumor status and to study patients on several occasions. Some studies look into the deeper levels of cellular energetics, beyond the phosphorylation of FDG (Project 1). Others measure tumor growth at the level of DNA replication (Project 2). The hormonal status of tumors is being characterized (Project 4), as are factors such as oxygenation that influence tumor biology as well as response to therapy (Project 3). Throughout the projects, metabolic imaging measurements are tested as predictors of important aspects of treatment outcome. In addition to providing insight into the metabolic response of a patient receiving standard surgical, drug or radiation therapy, PET imaging will provide human data on mechanisms of response in new cancer treatment strategies. As a result of these studies, metabolic images of regional tumor metabolism done before, during, and long after therapy are providing insight into tumor biology that is helping to select evaluate, and even modify therapy for the individual patient.